N-substituted 2,3,4,5,-tetrahydro-1h-3-benzazepines

ABSTRACT

N-substituted-2,3,4,5-tetrahydro-1H-3-benzazepines are prepared having pharmacological activity including analgesic and hypoglycemic action.

United States Patent Tokolics et al.

[ 1 June 20, 1972 [72] Inventors: Joseph Tokolics, King of Prussia;Gordon A. Hughes, Haverford; Herchel Smith,

Wayne, all of Pa.

{73] Assignee: American Home Products Corporation,

New York, NY.

[22] Filed: July 14, I969 [2|] Appl. No,: 860,449

Related US. Application Data [62] Division of Ser. No. 572,676, Aug. l6,I966, Pat. No.

[52] US. Cl. ..260/239 BB [51] Int. Cl. ...C07d 41/08 [58] Field ofSearch ..260/239 BB [56] References Cited UNITED STATES PATENTS3,258,459 6/1966 Yale et al ..260/239 3,055,883 9/l962 Mull ..260/239FOREIGN PATENTS OR APPLICATIONS 822,506 IO/l959 Great Britain ..260/239OTHER PUBLICATIONS Houben-Weyl, Methoden Der Organischen Chemie, Vol.ll/l (Stuttgart, 1957). pages 982- 985. OD 258H7.

Primary Examiner-Alton D. Rollins Attorney-John J. Hagan, John Legdey,Andrew Kaflto, Edmund H. O'Brien, Joseph Martin Weigman and Dwight J.Potter 57 ABSTRACT N-substituted-2,3 ,4,5-tetrahydrol H-3-benzazepinesare prepared having pharmacological activity including analgesic andhypoglycemic action.

10 Claims, No Drawings N-SUBSTITUTED 2,3,4,5 ,-TETRAHYDRO- l H-3-BENZAZEPINES The present application is a divisional application of Ser.No. 572,676, filed Aug. 16, 1966 now U.S. Pat. No. 3,483,185 issued Dec.9, 1969.

This invention relates to and has for its objects the provision of newphysiologically active compounds, novel processes for their productionand new intermediates useful in the preparation thereof.

More particularly, this invention relates to compounds of the fonnula(I):

and the acid-addition salts thereof, wherein hydrogen,

lower alkyl, lower alkoxy, benzyloxy, lower alkyl mercapto, di(loweralkyl)amino, halo or trifluoromethyl; n is one, two or three; and R isamino, di(lower alkyl)amino alkyl, carboximidoylguanidine, sulfonamoyland N,N-di(lower alkyl)sulfamoyl.

The terms lower alkyl and lower alkoxy, as employed herein, include bothstraight and branched chain radicals of less than eight carbon atoms.

As to salts, those coming within the purview of this invention includethe acid-addition salts, particularly the non-toxic acid-addition salts.Acids useful for preparing these acid-addition salts include, interalia, inorganic acids, such as the hydrohalic acids (e.g., hydrochloricacid and hydrobromic acid), sulfuric acid, nitric acid, boric acid andphosphoric acid, and organic acids such as maleic, methane sulfonic,cyclohexane sulfanic, tartaric, citric, acetic and succinic acid.

The compounds of this invention, including the acid-addition saltsthereof, are therapeutically active substances which are useful asanalgesic and hypoglycemic agents.

The compounds may be formulated for such administration, theconcentration and/or dosage being based on the activity of theparticular compound and the requirements of the patient.

The compounds of this invention can be prepared by a variety of methods.

One suitable method involves the reaction of a compound of the formula(II):

. wherein X and n are as hereinbefore defined, with a compound of theformula (lll):

R-(halo) wherein the halo is preferably chloro, and R is as hereinbeforedefined. A second method involves heating the compound of formula (II),or its salt, at elevated temperatures, with a sulfonarnide in a basicmedium. Another method involves reduc' ing a compound of the formula(IV):

wherein X and n are as hereinbefore defined, with a reducing agent, suchas lithium aluminum hydride, to yield a compound of the formula (V):

tetrahydro-7-halo-IH-S-benzazepine (e.g., 2,3,4,5-tetrahydro-7-chloro-lH-3-benzazepine); 2,3,4,5-tetrahydro-7-trifluoromethyl-lH-3-benzazepine; 2,3,4,5-tetrahydro-7-alkoxylH-3-benzazepine (e. g., 2,3,4,5-tetrahydro-7-methoxy-1 H-3-benzazepine);2,3,4,5-tetrahydro-7-lower alkyl-lH-3- benzazepine (e.g.,2,3,4,5-tetrahydro-7-methyl-1H-3- benzazepine 2,3,4,5-tetrahydro-8-benzyloxyl H -3- benzazepine;2,3,4,5-tetrahydro-8-di(lower alkyl)amino-ll-l- 3-benzazepine (e.g.,2,3,4,5-tetrahydro-8-dimethylamino-1H- 3-benzazepine);2,3,4,5-tetrahydro-8 -methylmercapto-lH-3- benzazepine;2,3,4,5-tetrahydro-7, 8-dihalo-1l-l-3- benzazepine e.g.2,3,4,5-tetrahydro-7,8-dichlorol H-3- benzazepine2,3,4,5-tetrahydro-7-halo-8-trifluoromethylll-l-3-benzazepine (e. g.,

EXAMPLE I 3-[ 3-( Dimethylamino )propyl ]-2,3 ,4,5-tetrahydro-1H-3-benzazepine, dihydrochloride A mixture of 2.0 gm. of2,3,4,5-tetrahydro-ll-l-3- benzazepine, 60.0 ml. of n-propanol, 2.0 gm.of potassium carbonate and 2.0 gm. of dimethylaminopropyl chloride isrefluxed for 5 hours. The mixture is cooled, filtered and the solvent isremoved by evaporation in vacuo. The residue is then dissolved in 10%sodium hydroxide solution and extracted with ether. The ether layer iswashed with water, brine, dried with sodium sulfate, and then treatedwith hydrogen chloride. The resulting precipitate is filtered andrecrystallized from ethanol to yield3-[3-(dimethylamino)propyl]-2,3,4,5- tetrahydro-lH-3-benzazepine,dihydrochloride having a melting point of 287290. Anal. Calcd. For C H NCl C,59.01; l-l,8.58; N,9.l7; C l,23.22; Found: C,58.82; H,8.76; N,9.25;Cl,23.00.

EXAMPLE 23-[3-(Dimethylamino)propyl]-7-chloro-2,3,4,5-tetrahydrolH-3-benzazepine,dihydrochloride Following the procedure of Example 1, but substituting2,3,4,5-tetrahydro-7-chloro-lH-3-benzazepine for 2,3, 4,5-tetrahydro-lH-Ii-benzazepine there is obtained 3-[3-(dimethylamino)propyl 7-chloro-2,3,4,5tetrahydro- 1 1+3 benzazepine,dihydrochloride.

EXAMPLE 33-[3-(Dimethylamino)propyl]-7-methyl-2,3,4,5-tetrahydrolH-3-benzazepine,dihydrochloride Following the procedure of Example 1, but substituting2,3,4,5-tetrahydro-7-methyl-lH-3-benzazepine for 2,3, 1,5-tetrahydro-lH-3-benzazepine there is obtained 3-[3-(dimethylamino)propyl] 7-methyl-2,3 ,4,5-tetrahydro- 11-1-3-benzazepine, dihydrochloride.

EXAMPLE 4 3-[ 3-( Dimethylamino)propyl ]-7-methoxy-2,3,4,5-tetrahydrolH-3-benzazepine, dihydrochloride Following the procedureof Example 1, but substituting2,3,4,5-tetrahydro-7-methoxy-lH-3-benzazepine for 2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 3-[3- (dimethylamino)propyl 7-methoxy-2,3 ,4,5-tetrahydrol H-3- benzazepine,dihydrochloride.

EXAMPLE 5 3- 3-( Dimethylamino )propyl ]-7-trifluoromethyl-2,3 ,4,5-tetrahydro-1 l-l-3-benzazepine, dihydrochloride Following the procedureof Example 1, but substituting 2,3 ,4,S-tetrahydro-7-trifluoromethyllH-3-benzazepine for 2,3,4,5-tetrahydro-lH-3-benzazepine there isobtained 3-[3- (dimethylamino)propyl]7-trifluorometyyl-2,3 ,4,5-tetrahydro-1H-3-benzazepine, dihydrochloride.

EXAMPLE 6 3-[3-(Dimethylamino)propyl]-7-benzyloxy-2,3,4,5- tetrahydro-lH-3-benzazepine, dihydrochloride Following the procedure of Example 1,but substituting 2,3,4,5-tetrahydro-7-benzyloxy- 1 H-3-benzazepine for2,3,4,5- tetrahydro-lH-3-benzazepine there is obtained 3-[3-(dimethylamino )propyl 7-benzyloxy-2,3 ,4,5-tetrahydrol H-3-benzazepine, dihydrochloride.

EXAMPLE 7 3-[ 3(Dimethylamino)propy1]-7,8-dichloro-2,3,4,5- tetrahydrolH-3-benzazepine, dihydrochloride Following the procedure of Example 1,but substituting 2 ,3,4,5-tetrahydro-7,8-dichlorol H-3-benzazepine for2,3.4,5-tetrahydro-lH-3-benzazepine there is obtained 3-[3-(dimethylamino)propyl 7,8-dichloro-2,3 ,4,5-tetrahydro-1H-3-benzazepine, dihydrochloride.

EXAMPLE 8 3-[3-(Dimethylamino)propyl]-7,8-dimethoxy-2,3,4,5- tetrahydrolH-3-benzazepine, dihydrochloride Following the procedure of Example 1,but substituting 2 ,3 ,4,5-tetrahydro-7 ,8-dimethoxyl H-S-benzazepinefor 2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 3-[3-(dimethylamino)propyl]7,8-dimethoxy-2,3,4,5-tetrahydrolH-3-benzazepine,dihydrochloride.

EXAMPLE 9 3-[3-(Dimethylamino)propyl]-7,8-dimethyl-2,3,4,5 tetrahydrolH-3-benzazepine, dihydrochloride Following the procedure of Example 1but substituting 2 ,3 ,4,5-tetrahydro-7,8-dimethyll H-3-benzazepine for2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 3-[3-(dimethylamino)propyl 1,7 ,8-dimethyl-2,3 ,4,5-tetrahydro-1H-3-benzazepine, dihydrochloride.

EXAMPLE l EXAMPLE 1 l [3-( 2,3 ,4,5 -Tetrahydro-7-chlorolH-3-benzazepine )carboximidoyl]guanidine, hydrochloride Following theprocedure of Example 10, but substituting2,3,4,5-tetrahydro-7-chloro-lH-B-benzazepine hydrochloride for2,3,4,5-tetrahydro-lH-3-benzazepine hydrochloride there obtained [3-( 2.3,4,5-tetrahydro-7-chloro-1H-3- benzazepine)carboximidoyl]guanidine,hydrochloride.

EXAMPLE l2 13-(2.3.4.5-Tetrahydro-7-methyllH-3-benzazepine)carboximidoyl ]guanidine, hydrochloride Following theprocedure of Example 10, but substituting 2,3 ,4,5-tetrahydro-7-methyllH-B-benzazepine hydrochloride for 2,3,4,5-tetrahydro-lH-3-benzazepinehydrochloride there is obtained [3-(2,3,4,5rtetrahydro-7-methyl-lH-3-benzazepine )carboximidoyl1guanidine, hydrochloride.

EXAMPLE l3 [3-( 2,3,4,5-Tetrahydro-7-methoxylH-3-benzazepine)carboximidoyl]guanidine, hydrochloride Following theprocedure of Example 10, but substituting 2,3,4,5 ,-tetrahydro7-methoxy-1 H-3-benzazepine hydrochloride for 2,3,4,5-tetrahydro-3-benzazepinehydrochloride there is obtained [3-(2,3,4,5-tetrahydro-7- methoxylH-3-benzazepine )carboximidoyl ]guanidine, hydrochloride.

EXAMPLE l4 [3-( 2,3,4,5Tetrahydro-7-benzyloxylH-3-benzazepine)carboximidoyljguanidine, hydrochloride Following theprocedure of Example 10, but substituting2,3,4,S-tetrahydro-I-benzyloxyl H-3-benzazepine hydrochloride for2,3,4,5-tetrahydro-lH-3-benzazepine hydrochloride there is obtained[3-(2,3,4,5-tetrahydro-7- benzyloxylH-3-benzazepine)carboximicloyl1guanidine, hydrochloride.

EXAMPLE l5 [3-( 2,3,4,5 -Tetrahydro-7-trifluoromethyll H-3- benzazepine)carboximidoyl ]guanidine, hydrochloride Following the procedure ofExample 10, but substituting 2 ,3 ,4,5-tetrahydro7-trifluoromethyllH-3-benzazepine hydrochloride for 2,3,4,5-tetrahydro-ll-l-3-benzazepinehydrochloride there is obtained [3-(2,3,4,5-tetrahydro-7-trifluoromethyll H-3-benzazepine )carboximidoyl guanidine,hydrochloride.

EXAMPLE 16 [3-( 2,3,4,5-Tetrahydro-7,8-dichlorol H-3 -benzazepine)carboximidoyljguanidine, hydrochloride Following the procedure ofExample 10, but substituting 2,3,4,5-tetrahydro-7,S-dichlorolH-3-benza2epine hydrochloride for 2,3,4,5-tetrahydro-lH-3-benzazepinehydrochloride there is obtained [3-(2,3,4,5-tetrahydro-7,8- dichloro- 1H-3-benzazepine)carboximidoyl guanidine, hydrochloride.

EXAMPLE [7 [3-( 2,3,4,5-Tetrahydro-7,8-dimethoxyl H-3-benzazepine)carboximidoyl] guanidine, hydrochloride Following the procedure ofExample 10, but substituting 2,3,4,5-tetrahydro-7,8-dimethoxylH-S-benzazepine hydrochloride for 2,3,4,5-tetrahydro-lH-3-benzazepinehydrochloride there is obtained [3-(2,3,4,5-tetrahydro-7,8- dimethoxy 1H-3-benzazepine )carboximidoyl] guanidine, hydrochloride.

EXAMPLE l8 [3-( 2,3,4,S-TetrahydroJfi-dimethyllH-3-benzazepine)carboximidoyl]guanidine, hydrochloride Following theprocedure of Example 10, but substituting 2,3,4,5-tetrahydro-7,8-dimethyll H-3-benzazepine hydrochloride for2,3,4,5-tetrahydro-lH-3-benzazepine hydrochloride there is obtained[3-(2,3,4,5-tetrahydro-7,8- dimethyll H-3-benzazepine)carboximidoyl]guanidine, hydrochloride.

EXAMPLE l92,3,4,5-Tetrahydro-N,N-dimethyl-lH-3-benzazepine-3-sulfonamide To amixture of 4.0 gm. of 2,3,4,5-tetrahydro-lH-3- benzazepine and 20 ml. oftoluene at --20 is slowly added 2,3 ,4,5-tetrahydro-7-trifluoromethyllH-3-benzazepine 1.96 gm. of N,N-dimethyl sulfonyl chloride. The mixtureis then stirred at room temperature for 18 hours. The solvent isevaporated in vacuo and the residue is recrystallized frommethanol-water to yield 2.64 gm. of 2,3,4,5-tetrahydro-N,N-dimethyl-lH-3-benzazepine-3-sulfonamide having a melting point of 108-1Anal. Calcd. for C,,H,,,N,o s: C,56.67; H,7.l3; N,ll.02; S,l2.60;

Found: C,56.88; H,7.26; N, 10.84; S,l2.65.

EXAMPLE 2O 2 ,3 ,4,5-Tetrahydro-7-chloro-N,N-dimethyl H-3-benzazepine-3-sulfonamide Following the procedure of Example 19, butsubstituting 2,3,4,5 tetrahydro-7-chloro-lH-3-benzazepine for 2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 2,3,4,5-tetrahydro-7-chloro-N,N-dimethyll H-3-benzazepine-3-sulfonamide.

EXAMPLE 2] 2 ,3 ,4,5-Tetrahydro-7-methyl-N,N-dimethyll H-3-benza2epine-3-sulfonamide Following the procedure of Example 19, butsubstituting 2,3,4,5-tetrahydro-7-methyl-lH-3-benzazepine for 2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 2,3,4,5-tetrahydro-7-methyl-N,N-dimethyll H-3-benzazepine-3-sulfonamide.

EXAMPLE 22 2,3,4,5-Tetrahydro-7-methoxy-N,N-dimethyl-lH-3-benzazepine-S-sulfonamide Following the procedure of Example 19, butsubstituting 2,3,4,5-tetrahydro-7-methoxy-lH-3-benzazepine for 2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 2,3,4,5-tetrahydro-7-methyl-N,N,-dimethyll H-3-benzazepine-3-sulfonamide.

EXAMPLE 23 2,3 ,4,5-Tetrahydro-7-trifluoromethyl-N,N-dimethyll l-l-3-benzazepine-3-sulfonamide Following the procedure of Example 19, butsubstituting for 2,3,4,5-tetrahydro-1H-3-benzazepine there is obtained 2,3 ,4,5-tetrahydro-7-trifluoromethyl-N,N-dimethyll H-3-benzazepine-3sulfonamide.

EXAMPLE 24 2,3,4,5-Tetrahydro-7,8-dichloro-N,N-dimethyl-lH-3-benzazepine-3-sulfonamide Following the procedure of Example 19, butsubstituting 2 ,3 ,4,S-tetrahydro-7,8-dichlorol H-3-benzazepine for2,3,4,5-tetrahydro-l H3-benzazepine there is obtained 2,3,4,5-tetrahydro-7,8-dichloro-N,N-dimethyll H-3 -benzazepine-3 sulfonamide.

EXAMPLE 25 2,3 ,4,5-Tetrahydro-7,8-dimethoxy-N,N-dimethyll H-3-benzazepine-3-sulfonamide Following the procedure of Example 19, butsubstituting 2,3,4,5-tetrahydro-7,8-dimethoxyl H-3-benzazepine for2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 2,3,4,5-tetrahydr0-7,8-dimethoxy-N,N-dimethyll H-3- benzazepine-3-sulfonamide.

EXAMPLE 26 2 ,3 ,4,5-Tetrahydro-7,8-dimethyl-N,N-dimethyll H-3-benzazepine-3-sulfonamide Following the procedure of Example 19, butsubstituting 2,3 ,4,5-tetrahydro-7,B-dimethyll H-3-benzazepine for2,3,4,5-tetrahydro-ll-l-3-benzazepine there is obtained 2,3,4,5-tetrahydro-7,8-dimethyl-N,N-dimethyll H-3-benzazepine-3-sulfonamide.

EXAMPLE 27 EXAMPLE 28 2,3,4,5-Tetrahydro-7-chlorolH-3-benzazepine-3-sulfonamide.

Following the procedure of Example 27, but substituting2,3,4,5-tetrahydro-7-chloro-lH-3-benzazepine for 2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 2,3,4,5-tetrahydro-7-chlorol H-3-benzazepine-3-sulfonamide.

EXAMPLE 29 2,3 ,4,5-Tetrahydro-7-methyl-1H-3-benzazepine-3-sulfonamide.

Following the procedure of Example 27, but substituting2,3,4,5-tetrahydro-7-methyl-lH-3-benzazepine for. 2,3, 1,5-tetrahydro-lH-3-benzazepine there is obtained 2,3,45-tetrahydro-7-methyll H-3 -benzazepine-3-sulfonamide.

EXAMPLE 30 2,3,4,5-Tetrahydro-7-methoxy-l H-3-benzazepine-3-sulfonamide.

Following the procedure of Example 27, but substituting2,3,4,5-tetrahydro-7-methoxy-lH-3-benzazepine for 2,3,4,5,-tetrahydro-lH-3-benzazepine there is obtained 2,3,4,5-tetrahydro-7-methoxyl H-3-benzazepine-3-sulfonamide,

EXAMPLE 3] 2,3,4,5-Tetrahydro-7-trifluoromethyl-lH-3-benzazepine-3-sulfonamide.

Following the procedure of Example 27, but substituting 2,3,4,5-tetrahydro-7-trifluoromethyl- 1 H-3-benzazepine for2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained2,3,4,5-tetrahydro-7-trifluoromethyll H-3 -benzazepine-3-sulfonamide.

EXAMPLE 32 2 ,3 ,4,5-Tetrahydro-7,8-dichlorol H-3-benzazepine-3-sulfonamide.

Following the procedure of Example 27, but substituting,2,3,4,5-tetrahydro-7,8dichlorol H-3-benzazepine for2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained2,3,4,5-tetrahydro-7,8-dichlorol H-3-benzazepine-3-sulfonamide.

EXAMPLE 33 2,3,4,5-Tetrahydro-7,8-dimethoxylH-3-benzazepine-3-sulfonamide Following the procedure of Example 27, butsubstituting 2,3,4,5-tetrahydro-7,8-dimethoxyl H-3-benzazepine for2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained2,3,4,5-tetrahydro-7,8-dimethoxyl H-3-benzazepine-3-sulfonamide.

EXAMPLE 34 2,3,4,5-Tetrahydro-7,8-dimethyllH-3-benzazepine-3-sulfonamide of 2,3,4,5-tetrahydro-1H-3- I Followingthe procedure of Example 27, but substituting 2,3,4,5-tetrahydroo7,8-dimethyll H-3-benzazepine for2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 2,3 ,4,5-tetrahydro-7,S-dimethyll H-3-benzazepine-3-sulfonamide.

EXAMPLE 35 3-Amino-2,3,4,5-tetrahydro-l H-3-benzazepine, hydrochloride Asolution of 2,3,4,5-tetrahydro-lH-3-benzazepine' hydrochloride (2.0 g.)in hydrochloric acid (4.0 ml.) is added dropwise to a solution of sodiumnitrite (2.0 g.) in water (4.0 ml.) at 0. After standing at 25 for 2hours the product is filtered and recrystallized from aqueous methanolto give N- nitrono-2,3,4,5-tetrahydro-lH-3-benzazepine (1.25 g.) m.p.6467.

To a solution of 0.7 gm. of N-nitroso-2,3,4,5-tetrahydrolH-3-benzazepinein ml. of ether at l0 is added 0.25 gm. of lithium aluminum hydride in10 ml. of ether. After standing at 10 for 1 hour, the excess lithiumaluminum hydride is decomposed by adding 10 ml. of wet tetrahydrofuranfollowed EXAMPLE 36 3-Amino-2,3,4,5-tetrahydro-7-chlorolH-3-benzazepine, hydrochloride Following the procedure of Example 35,but substituting 2,3,4,5-tetrahydro-7-chloro-lH-3-benzazepine forN-nitroso- 2,3,4,5-tetrahydro-lH-S-benzazepine there is obtained 3-amino-2, 3 ,4,5-tetrahydro-7-chlorol H-3-benzazepine, hydrochloride.

EXAMPLE 37 3 -Amino-2,3 ,4,5-tetrahydro-7-methyll H-3-benzazepine,hydrochloride Following the procedure of Example 35, but substituting2,3,4,5-tetrahydro-7-methyl-lH-3-benzazepine for 2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 3-amino-2,3,4,5-tetrahydro-7-methyll H-3-benzazepine, hydrochloride.

EXAMPLE 3 8 3-Amino-2,3,4,5-tetrahydro-7-trifluoromethyl-lH-3-benzazepine, hydrochloride Following the procedure of Example 35, butsubstituting 2,3,4,5-tetrahydro-7-trifluoromethyll H-3benzazepine for2,3,4,5-tetrahydro-ll-I-3-benzazepine there is obtained 3-amino-2,3,4,5-tetrahydro-7-trifluoromethyll H-3- benzazepine,hydrochloride.

EXAMPLE 39 3-Amino-2,3 ,4,5-tetrahydro-7-methoxyl H-3-benzazepine,hydrochloride Following the procedure of Example 35, but substituting2,3,4,5-tetrahydro-7-methoxy-lH-3-benzazepine for 2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 3-amino-2,3,4,5-tetrahydro-7-methoxy-l H-B-benzazepine, hydrochloride.

, 2,3,4,5-tetrahydro-7,S-dimethyll H-3-benzazepine EXAMPLE 403-Amino-2,3,4,5-tetrahydro-7-benzyloxyl H-3-benzazepine, hydrochlorideFollowing the procedure of Example 35, but substituting2,3,4,5-tetrahydro-7-benzyloxyl H-3-benzazepine for 2,3, 1,5-tetrahydro-lH-3-benzazepine there is obtained 3-amino-2,3,4,5-tetrahydro-7-benzyloxyl H-3-ben2azepine, hydrochloride.

EXAMPLE 4! EXAMPLE 42 3-Amino2,3,4,5-tetrahydro-7,8-dimethoxy-l H-3-benzazepine, hydrochloride Following the procedure of Example 35, butsubstituting 2,3,4,5-tetrahydro-7,S-dimethoxyl H-3-benzazepine for2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 3amino-2,3,4,5-tetrahydro-7,8-dimethoxyl H-3-benzazepine, hydrochloride.

EXAMPLE 43 3-Amino-2,3,4,5-tetrahydro-7,B-dimethyll H-3-benzazepine,hydrochloride Followingv the procedure of Example 35, but substitutingfor 2,3,4,5-tetrahydro-lH-3-benzazepine there is obtained 3- amino-2,3,4,5tetrahydro-7,8-dimethyll H-3-benzazepine, hydrochloride.

It is understood that the acid-addition salts of Examples 1 through 18and 35 through 43 can be converted to their free bases by anyconventional means.

The invention may be variously otherwise embodied within the scope ofthe appended claims.

What is claimed is: I

1. A compound selected from the group consisting of a compound of theformula:

(X) n N R and the non-toxic acid-addition salts thereof, wherein X isselected from the group consisting of hydrogen, lower alkyl, loweralkoxy, benzyloxy, lower alkyl mercapto, di(lower alkyl)amino, halo andtrifluoromethyl; n is a positive integer less than three; and R isselected from the group consisting of amino, di( lower alkyl) aminoalkyl, and carboximidoyl guanidine. v

2. A compound according to claim 1 which comprises the n0n-toxicacid-addition salts of 3-[3-(dimethylamino)propyl1- 2 ,3,4,5-tetrahydrol H-3-benzazepine.

3. A compound according to claim 1 which comprises the non-toxicacid-addition salts of 3-[3-(dimethylamino)propyl]- 2,3,4,5-tetrahydro-7-methoxyl H-3-benzazepine.

4. A compound according to claim 1 which comprises the non-toxicacid-addition salts of 3-[ 3-( dimethylamino)propyl]2,3,4,5-tetrahydro-7-chlorol H-3-benzazepine.

5. A compound according to claim 1 which comprises the non-toxicacid-addition salts of 3-[3-(dimethylamino)propyl]- 2,3,4,5-tetrahydro-7,8-dinitrol H-S-benzazepine.

6. A compound according to claim 1 which comprises the non-toxicacidaddition salts of 3-[3-(dimethylamino)propyl]-2,3,4,5-tetrahydro-7,8-dimethoxy-l H-3-benzazepine.

7. A compound which comprises the non-toxic acid-addition salts of3-amino-2,3,4,5-tetrahydrol H-3-benzazepine.

(X) n N-R and the non-toxic acid-addition salts thereof, wherein X isselected from the group consisting of hydrogen, lower alkyl, loweralkoxy, benzyloxy, lower alkylrnercapto, di(lower alkyl)amino, halo andtrifluoromethyl; n is a positive integer less than three; and R isamino.

[0. A compound selected from the group consisting of a compound of theformula:

and the non-toxic acid-addition salts thereof, wherein X is selectedfrom the group consisting of hydrogen, lower alkyl, lower alkoxy,benzyloxy, lower alkyl mercapto, di( Lower alkyl) amino, halo andtrifluoromethyl; n is a positive integer less than 3; and R iscarboximidoylguanidine.

2. A compound according to claim 1 which comprises the non-toxicacid-addition salts of3-(3-(dimethylamino)propyl)-2,3,4,5-tetrahydro-1H-3-benzazepine.
 3. Acompound according to claim 1 which comprises the non-toxicacid-addition salts of3-(3-(dimethylamino)propyl)-2,3,4,5-tetrahydro-7-methoxy-1H-3-benzazepine.4. A compound according to claim 1 which comprises the non-toxicacid-addition salts of 3-(3-(dimethylamino)propyl)-2,3,4,5-tetrahydro-7-chloro-1H-3-benzazepine.
 5. A compound accordingto claim 1 which comprises the non-toxic acid-addition salts of3-(3-(dimethylamino)propyl)-2,3,4,5-tetrahydro-7,8-dinitro-1H-3-benzazepine.6. A compound according to claim 1 which comprises the non-toxicacid-addition salts of3-(3-(dimethylamino)propyl)-2,3,4,5-tetrahydro-7,8-dimethoxy-1H-3-benzazepine.
 7. A compound which comprises the non-toxic acid-additionsalts of 3-amino-2,3,4,5-tetrahydro-1H-3-benzazepine.
 8. A compoundwhich comprises the non-toxic acid-addition salts of(3-amino-2,3,4,5-tetrahydro-1H-3-benzazepine) carbo-ximidoyl) guanidine.9. A compound selected from the group consisting of a compound of theformula: and the non-toxic acid-addition salts thereof, wherein X isselected from the group consisting of hydrogen, lower alkyl, loweralkoxy, benzyloxy, lower alkyl mercapto, di(lower alkyl)amino, halo andtrifluoromethyl; n is a positive integer less than 3; and R is amino.10. A compound selected from the group consisting of a compound of theformula: and the non-toxic acid-addition salts thereof, wherein X isselected from the group consisting of hydrogen, lower alkyl, loweralkoxy, benzyloxy, lower alkyl mercapto, di(Lower alkyl) amino, halo andtrifluoromethyl; n is a positive integer less than 3; and R iscarboximidoylguanidine.